accelerators Research Update from Rachel Guerra, PhD, UMDF Funded Runner-Up from Big Pitch 2019

Press Room, Research News

accelerators logo Research Update

At the very first The Big Pitch Event at the UMDF Symposium for Mitochondrial Medicine in 2019, three candidates had five minutes each to present their research projects over a live webcast. When the online voting concluded, Dr. Arwen Gao of Ecole Polytechnique Federale de Lausanne in Lausanne Switzerland was selected as the 2019 accelerators $50,000 prize winner. But then, something amazing happened.  Before Dr. Gao was announced as the winner, two accelerators donor families said they were incredibly inspired by all of the presentations and wanted to see all of their projects continue for the entire patient community. The William Wright Family Foundation and The Logan Sloane Aronson Research Fund in honor of Sydney Breslow each committed $50,000 to fund the projects of the two runners-up: Dr. Rachel Guerra of the Morgridge Institute for Research in Madison, WI, and Dr. Zachary Wilson, University of Utah at Salt Lake City.

We recently caught up with Dr. Rachel Guerra to see how her research has progressed since 2019. She graciously provided the following update:

Since my Post-Doctoral UMDF accelerator runner-up award, I have transitioned to the position of Staff Scientist in the Pagliarini Laboratory at Washington University in St. Louis. In this role, I am excited to continue to study open questions in coenzyme (CoQ) biosynthesis, while using my expertise in biochemistry and mass spectrometry to support existing, impactful projects in the lab while also mentoring the next generation of scientists.

During my UMDF fellowship, I worked on a collaborative project to understand how the uncharacterized protein COQ9 contributes to CoQ biosynthesis and supports the formation of complex Q. Using cryogenic electron microscopy, we have provided the first structural characterization of a subcomplex of CoQ proteins: COQ9 and COQ7. This structure, along with molecular dynamics simulations, supports a model in which COQ9 cooperates with COQ7 to access CoQ precursors within the mitochondrial membrane to coordinate synthesis steps to produced mature CoQ. We have communicated these findings in a manuscript that has been recently accepted at Molecular Cell [a peer-review research journal] and will be published soon.

We have been interested in studying CoQ as its deficiency is a hallmark of mitochondrial disorders, yet many details of its transport remain unclear, thus thwarting the development of new, more effective CoQ-based therapeutics that don’t suffer from the same poor bioavailability of CoQ itself. By understanding how proteins come together at a structural level to make CoQ, we hope to gain insight to ways in which we could re-stabilize an unstable complex Q or bypass broken biosynthetic pathways in order to therapeutically address CoQ deficiencies for patients with mitochondrial disorders.

Rachel Guerra, PhD

We congratulate Dr. Guerra and her team on their work on the structural characterization of COQ9 and COQ7, and we are excited to see the upcoming published article!

The Pagliarini Lab, where Dr. Guerra works as Staff Scientist, has been a great supporter of UMDF Energy for Life Walkathons, first in southern Wisconsin and now in St. Louis. As Dr. Guerra said, “It was great to take part in the local EFL Walk/Run and meet mito families in the St Louis area!”

The United Mitochondrial Disease Foundation is committed to advancing the best, peer-reviewed science from around the world. To learn more about becoming an accelerator and other research funded, visit www.umdf.org/accelerators.